tbuckley/cabot-search huggingface dataset:
Flashback Foreword: Anti-HER2 Monoclonal Antibody as a Single Agent
Authors: Pamela J. Goodwin
Journal: Journal of Clinical Oncology (2023)

Article Tools FLASHBACK FOREWORD Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease. February 28, 2023 ARTICLE CITATION DOI: 10.1200/JCO.22.02679 Journal of Clinical Oncology - published online before print March 7, 2023 PMID: 36881997 Flashback Foreword: Anti-HER2 Monoclonal Antibody as a Single Agent Pamela J. Goodwin , MD, MSc1,2xPamela J. GoodwinSearch for articles by this author Show More 1Department of Medicine, Sinai Health System, University of Toronto, Toronto, Ontario, Canada2Former Associate Editor, Journal of Clinical Oncology, Alexandria, VA https://doi.org/10.1200/JCO.22.02679 First Page Full Text PDF Figures and Tables © 2023 by American Society of Clinical OncologyTHE TAKEAWAYIn 1999, Cobleigh et al1 demonstrated important activity of a single-agent recombinant humanized monoclonal antibody (now known as trastuzumab) targeting the human epidermal growth factor receptor (HER2) in women with pretreated metastatic HER2-positive breast cancer. This, along with subsequent studies of trastuzumab and other agents targeting HER2 in the metastatic and (neo)adjuvant settings, has revolutionized the management of HER2-positive breast cancer, leading to dramatic improvements in outcomes in both the early and metastatic settings.AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTERESTFlashback Foreword: Anti-HER2 Monoclonal Antibody as a Single AgentThe following represents disclosure information provided by the author of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).Pamela J. GoodwinResearch Funding: Epic Sciences (Inst)No other potential conflicts of interest were reported. Companion Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease
Multinational Study of the Efficacy and Safety of Humanized Anti-HER2 Monoclonal Antibody in Women Who Have HER2-Overexpressing Metastatic Breast Cancer That Has Progressed After Chemotherapy for Metastatic Disease
Authors: Melody A. Cobleigh, Charles L. Vogel, Debu Tripathy, Nicholas J. Robert, Susy Scholl, Louis Fehrenbacher, Janet M. Wolter, Virginia Paton, Steven Shak, Gracie Lieberman, Dennis J. Slamon
Journal: Journal of Clinical Oncology (2023)

Overexpression of the HER2 protein occurs in 25% to 30% of human breast cancers and leads to a particularly aggressive form of the disease. Efficacy and safety of recombinant humanized anti-HER2 monoclonal antibody as a single agent was evaluated in women with HER2-overexpressing metastatic breast cancer that had progressed after chemotherapy for metastatic disease.
Efficacy of antivirals and bivalent mRNA vaccines against SARS-CoV-2 isolate CH.1.1
Authors: Ryuta Uraki, Mutsumi Ito, Maki Kiso, Seiya Yamayoshi, Kiyoko Iwatsuki-Horimoto, Yuko Sakai-Tagawa, Yuri Furusawa, Masaki Imai, Michiko Koga, Shinya Yamamoto, Eisuke Adachi, Makoto Saito, Takeya Tsutsumi, Amato Otani, Yukie Kashima, Tetsuhiro Kikuchi, Hiroshi Yotsuyanagi, Yutaka Suzuki, Yoshihiro Kawaoka
Journal: The Lancet Infectious Diseases (2023)
Severe COVID-19 outcomes by cardiovascular risk profile in England in 2020: a population-based cohort study
Authors: Charlotte Warren-Gash, Jennifer A. Davidson, Helen Strongman, Emily Herrett, Liam Smeeth, Judith Breuer, Amitava Banerjee
Journal: The Lancet Regional Health - Europe (2023)

While cardiovascular disease (CVD) is a risk factor for severe COVID-19, the association between predicted cardiovascular risk and severe COVID-19 among people without diagnosed CVD is unclear.We carried out historical, population-based cohort studies among adults aged 40-84 years in England using linked data from the Clinical Practice Research Datalink. Individuals were categorized into: existing CVD, raised cardiovascular risk (defined using QRISK3 score ≥10%) and low risk (QRISK3 score <10%) at 12/03/2020. We described incidence and severe outcomes of COVID-19 (deaths, intensive care unit [ICU] admissions, hospitalisations, major adverse cardiovascular events [MACE]) for each group. Among those with a COVID-19 record to 31/12/2020, we re-classified cardiovascular risk at infection and assessed the risk of severe outcomes using multivariable Cox regression with complete case analysis. We repeated analyses using hypertension to define raised cardiovascular risk.Among 6,059,055 individuals, 741,913 (12.2%) had established CVD, 1,929,627 (31.8%) had a QRISK3 score ≥10% and 3,387,515 (55.9%) had a QRISK3 score <10%. Marked gradients were seen in the incidence of all severe COVID-19 outcomes by cardiovascular risk profile. Among those with COVID-19 (N = 146,760), there was a strong association between raised QRISK3 score and death: adjusted hazard ratio [aHR] 8.77 (7.62-10.10), N = 97,725, which remained present, though attenuated in age-stratified results. Risks of other outcomes were also higher among those with raised QRISK3 score: aHR 3.66 (3.18-4.21) for ICU admissions, 3.38 (3.22-3.56) for hospitalisations, 5.43 (4.44-6.64) for MACE. When raised cardiovascular risk was redefined by hypertension status, only the association with MACE remained: aHR 1.49 (1.20-1.85), N = 57,264.Individuals without pre-existing CVD but with raised cardiovascular risk (by QRISK3 score) were more likely to experience severe COVID-19 outcomes and should be prioritised for prevention and treatment. Addressing cardiovascular risk factors could improve COVID-19 outcomes.BMA Foundation for Medical Research/Rosetrees Trust, Wellcome, BHF.
Creating a semi-opened micro-cavity ovary through sacrificial microspheres as an in vitro model for discovering the potential effect of ovarian toxic agents
Authors: Min Ye, Yiran Shan, Bingchuan Lu, Hao Luo, Binhan Li, Yanmei Zhang, Zixuan Wang, Yuzhi Guo, Liliang Ouyang, Jin Gu, Zhuo Xiong, Ting Zhang
Journal: Bioactive Materials (2023)

The bio-engineered ovary is an essential technology for treating female infertility. Especially the development of relevant in vitro models could be a critical step in a drug study. Herein, we develop a semi-opened culturing system (SOCS) strategy that maintains a 3D structure of follicles during the culture. Based on the SOCS, we further developed micro-cavity ovary (MCO) with mouse follicles by the microsphere-templated technique, where sacrificial gelatin microspheres were mixed with photo-crosslinkable gelatin methacryloyl (GelMA) to engineer a micro-cavity niche for follicle growth. The semi-opened MCO could support the follicle growing to the antral stage, secreting hormones, and ovulating cumulus-oocyte complex out of the MCO without extra manipulation. The MCO-ovulated oocyte exhibits a highly similar transcriptome to the in vivo counterpart (correlation of 0.97) and can be fertilized. Moreover, we found that a high ROS level could affect the cumulus expansion, which may result in anovulation disorder. The damage could be rescued by melatonin, but the end of cumulus expansion was 3h earlier than anticipation, validating that MCO has the potential for investigating ovarian toxic agents in vitro. We provide a novel approach for building an in vitro ovarian model to recapitulate ovarian functions and test chemical toxicity, suggesting it has the potential for clinical research in the future.
Global epidemiology and disparities in atopic dermatitis
Authors: Anisa Mosam, Gail Todd
Journal: British Journal of Dermatology (2023)

Abstract Atopic dermatitis (AD) affects children and adults worldwide. Advancements have been made towards unravelling the pathogenesis of AD, identifying various triggers, linking the environment and psychosocial factors with disease and the development of therapeutic targets to improve disease control. This article describes the global epidemiology of AD and the disparities that exist in various populations and regions across the globe. AD prevalence and burden varies widely both within and between countries inhabited by the same ethnic groups, which suggests strong environmental influences in disease expression, with socioeconomic status and affluence considered to be the main driving factors. Inequities in access to healthcare, and the quality of healthcare provided, among racial and ethnic minority groups are well documented. Disparities in access to various topical and systemic therapies are affected by barriers to registration and approval, cost, manufacturing, supply and approval by medical insurance companies and governments. Identifying the factors driving the inequities in access to healthcare is central to achieving better patient care.
Optimizing biliary stenting in patients with distal malignant biliary obstruction
Authors: Marianna Arvanitakis
Journal: Endoscopy (2023)

Endoscopic biliary stenting plays a crucial part in the management of patients with malignant biliary strictures (MBSs), not only in a palliative setting where there is metastatic disease, but also in allowing neoadjuvant chemotherapy to be given before surgery [1]. The use of self-expandable metal stents (SEMSs) is preferred to plastic stents, as SEMSs are associated with a longer patient survival, a lower risk of stent dysfunction/cholangitis, and fewer reinterventions [1]. Fully covered SEMSs (FCSEMSs) have the advantage of being less prone to obstruction owing to tissue ingrowth, which allows easier stent removal; on the other hand, migration, into the duodenal lumen or even in an intrabiliary direction, can be of a major concern [2]. Neoadjuvant chemotherapy seems to be an additional risk factor that favors migration, which relates to the reduction in tumoral tissue [3]. Another debatable concern with the use of FCSEMSs is the incidence of cholecystitis, especially in patients presenting with tumor involvement of the cystic duct [3].
Corrigendum to “1773P Prediction of chemotherapy response in muscle-invasive bladder cancer: A machine learning approach”
Authors: E. Shkolyar, H. Bhambhvani, E. Tiu, V. Krishna, V. Krishna, V. Nimgaonkar, R. Krishnan, O. O’Donoghue, D. Vrabac, C-S. Kao, A. Joshi, J. Shah
Journal: Annals of Oncology (2023)
Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review
Authors: Diogo Libânio, Pedro Pimentel-Nunes, Barbara Bastiaansen, Raf Bisschops, Michael J. Bourke, Pierre H. Deprez, Gianluca Esposito, Arnaud Lemmers, Philippe Leclercq, Roberta Maselli, Helmut Messmann, Oliver Pech, Mathieu Pioche, Michael Vieth, Bas L.A.M. Weusten, Lorenzo Fuccio, Pradeep Bhandari, Mario Dinis-Ribeiro
Journal: Endoscopy (2023)

Abstract ESGE suggests conventional endoscopic submucosal dissection (ESD; marking and mucosal incision followed by circumferential incision and stepwise submucosal dissection) for most esophageal and gastric lesions. ESGE suggests tunneling ESD for esophageal lesions involving more than two-thirds of the esophageal circumference. ESGE recommends the pocket-creation method for colorectal ESD, at least if traction devices are not used. The use of dedicated ESD knives with size adequate to the location/thickness of the gastrointestinal wall is recommended. It is suggested that isotonic saline or viscous solutions can be used for submucosal injection. ESGE recommends traction methods in esophageal and colorectal ESD and in selected gastric lesions. After gastric ESD, coagulation of visible vessels is recommended, and post-procedural high dose proton pump inhibitor (PPI) (or vonoprazan). ESGE recommends against routine closure of the ESD defect, except in duodenal ESD. ESGE recommends corticosteroids after resection of &gt; 50 % of the esophageal circumference. The use of carbon dioxide when performing ESD is recommended. ESGE recommends against the performance of second-look endoscopy after ESD. ESGE recommends endoscopy/colonoscopy in the case of significant bleeding (hemodynamic instability, drop in hemoglobin &gt; 2 g/dL, severe ongoing bleeding) to perform endoscopic hemostasis with thermal methods or clipping; hemostatic powders represent rescue therapies. ESGE recommends closure of immediate perforations with clips (through-the-scope or cap-mounted, depending on the size and shape of the perforation), as soon as possible but ideally after securing a good plane for further dissection.
Artificial intelligence and the push for small adenomas: all we need?
Authors: Katharina Zimmermann-Fraedrich, Thomas Rösch
Journal: Endoscopy (2023)

Artificial intelligence (AI) has been enthusiastically welcomed by the endoscopic community, although many of the potential applications have remained in the testing environment using images and videos, and have not been tested in the clinical setting. Some computer-aided polyp detection (CADe) systems have entered the field of clinical application, however, and have been studied extensively in randomized trials. At the time of writing, 19 such trials were available as full publications [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]. They all show a more or less significant increase in detection of small adenomas. The same results are summarized over and over again in no less than 16 meta-analyses [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35], plus a protocol for a further one [36], as well as a meta-analysis of some of these meta-analyses [37]!
ATRX, a guardian of chromatin
Authors: Paula Aguilera, Andrés J. López-Contreras
Journal: Trends in Genetics (2023)

ATRX (alpha-thalassemia mental retardation X-linked) is one of the most frequently mutated tumor suppressor genes in human cancers, especially in glioma, and recent findings indicate roles for ATRX in key molecular pathways, such as the regulation of chromatin state, gene expression, and DNA damage repair, placing ATRX as a central player in the maintenance of genome stability and function. This has led to new perspectives about the functional role of ATRX and its relationship with cancer. Here, we provide an overview of ATRX interactions and molecular functions and discuss the consequences of its impairment, including alternative lengthening of telomeres and therapeutic vulnerabilities that may be exploited in cancer cells.
Polymer- and lipid-based nanocarriers for ocular drug delivery: Current status and future perspectives
Authors: Haijie Han, Su Li, Mingyu Xu, Yueyang Zhong, Wenjie Fan, Jingwei Xu, Tinglian Zhou, Jian Ji, Juan Ye, Ke Yao
Journal: Advanced Drug Delivery Reviews (2023)

Ocular diseases seriously affect patients' vision and life quality, with a global morbidity of over 43 million blindness. However, efficient drug delivery to treat ocular diseases, particularly intraocular disorders, remains a huge challenge due to multiple ocular barriers that significantly affect the ultimate therapeutic efficacy of drugs. Recent advances in nanocarrier technology offer a promising opportunity to overcome these barriers by providing enhanced penetration, increased retention, improved solubility, reduced toxicity, prolonged release, and targeted delivery of the loaded drug to the eyes. This review primarily provides an overview of the progress and contemporary applications of nanocarriers, mainly polymer- and lipid-based nanocarriers, in treating various eye diseases, highlighting their value in achieving efficient ocular drug delivery. Additionally, the review covers the ocular barriers and administration routes, as well as the prospective future developments and challenges in the field of nanocarriers for treating ocular diseases.
Role of immune responses in the development of NAFLD-associated liver cancer and prospects for therapeutic modulation
Authors: Neda Yahoo, Michael Dudek, Percy Knolle, Mathias Heikenwälder
Journal: Journal of Hepatology (2023)

The liver is the central metabolic organ of the body, regulating energy and lipid metabolism, while also having potent immunological functions. Overwhelming the metabolic capacity of the liver via obesity and a sedentary lifestyle leads to hepatic lipid accumulation, chronic necro-inflammation, enhanced mitochondrial/endoplasmic reticulum stress and development of non-alcoholic fatty liver disease (NAFLD), and its more severe form non-alcoholic steatohepatitis (NASH). Based on an improved understanding of pathophysiological mechanisms, specifically targeting metabolic pathways to prevent or slow down the progression of NAFLD to liver cancer will become possible. Genetic/environmental factors are also known to contribute to the development of NASH and progression to liver cancer. The complex pathophysiology of NAFLD-NASH is reflected by environmental factors, particularly the gut microbiome and its metabolic products. NAFLD-associated HCC most often occurs in the context of a chronically inflamed and cirrhotic liver. Recognition of environmental alarmins or metabolites derived from the gut microbiota and the metabolically injured liver create a strong inflammatory milieu supported by innate and adaptive immunity. Several recent studies indicate that chronic steatosis induces auto-aggressive CD8+CXCR6+PD1+ T cells that eliminate parenchymal and non-parenchymal cells in an antigen-independent manner. This promotes chronic liver damage and a pro-tumorigenic environment. CD8+CXCR6+PD1+ T cells possess an exhausted, hyperactivated, resident phenotype; they trigger the NASH to HCC transition and might be responsible for weaker responses to immune checkpoint inhibitors - in particular atezolizumab/bevacizumab. Here, we provide an overview of NASH-related inflammation/pathogenesis, focusing on new discoveries on the role of T cells. This review discusses preventive measures to halt disease progression to liver cancer and therapeutic strategies to manage patients with NASH-HCC.
Deregulated intracellular pathways define novel molecular targets for HBV-specific CD8 T cell reconstitution in chronic hepatitis B
Authors: Ilaria Montali, Camilla Ceccatelli Berti, Marco Morselli, Greta Acerbi, Valeria Barili, Giuseppe Pedrazzi, Barbara Montanini, Carolina Boni, Arianna Alfieri, Marco Pesci, Alessandro Loglio, Elisabetta Degasperi, Marta Borghi, Riccardo Perbellini, Amalia Penna, Diletta Laccabue, Marzia Rossi, Andrea Vecchi, Camilla Tiezzi, Valentina Reverberi, Chiara Boarini, Gianluca Abbati, Marco Massari, Pietro Lampertico, Gabriele Missale, Carlo Ferrari, Paola Fisicaro
Journal: Journal of Hepatology (2023)
Effect of Prior Local Therapy on Response to First-line Androgen Receptor Axis Targeted Therapy in Metastatic Castrate-resistant Prostate Cancer: A Secondary Analysis of the COU-AA-302 Trial
Authors: Soumyajit Roy, Yilun Sun, Scott C. Morgan, Christopher J.D. Wallis, Kevin King, Yu M. Zhou, Leah A. D'souza, Omar Azem, Adrianna E. Cueto-Marquez, Nathaniel B. Camden, Daniel E. Spratt, Amar U. Kishan, Fred Saad, Shawn Malone
Journal: European Urology (2023)
Anti–G Protein–Coupled Receptor, Class C Group 5 Member D Chimeric Antigen Receptor T Cells in Patients With Relapsed or Refractory Multiple Myeloma: A Single-Arm, Phase Ⅱ Trial
Authors: Jieyun Xia, Hujun Li, Zhiling Yan, Dian Zhou, Ying Wang, Yuekun Qi, Jiang Cao, Depeng Li, Hai Cheng, Wei Sang, Feng Zhu, Haiying Sun, Wei Chen, Kunming Qi, Dongmei Yan, Tingting Qiu, Jianlin Qiao, Ruosi Yao, Yang Liu, Xue Wang, Yanlei Zhang, Shuixiu Peng, Chih-Hua Huang, Junnian Zheng, Zhenyu Li, Alex H. Chang, Kailin Xu
Journal: Journal of Clinical Oncology (2023)

G protein-coupled receptor, class C group 5 member D (GPRC5D) is considered to be a promising surface target for multiple myeloma (MM) immunotherapy. Here, we report the efficacy and safety of anti-GPRC5D chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory (R/R) MM.This phase Ⅱ, single-arm study enrolled patients (18-70 years) with R/R MM. Lymphodepletion was performed before patients received 2 × 106/kg anti-GPRC5D CAR T cells. The primary end point was the proportion of patients who achieved an overall response. Safety was also evaluated in eligible patients.From September 1, 2021, to March 23, 2022, 33 patients were infused with anti-GPRC5D CAR T cells. At a median follow-up of 5.2 months (range, 3.2-8.9), the overall response rate was 91% (95% CI, 76 to 98; 30 of 33 patients), including 11 (33%) stringent complete responses, 10 (30%) complete responses, four (12%) very good partial responses, and five (15%) partial responses. Partial responses or better were observed in nine (100%) of nine patients with previous anti-B-cell maturation antigen (BCMA) CAR T-cell therapy, including two patients who had received repeated anti-BCMA CAR T-cell infusions with no responses at the last time. Grade 3 or higher hematologic toxicities were neutropenia (33 [100%]), anemia (17 [52%]), and thrombocytopenia (15 [45%]). Cytokine release syndrome occurred in 25 (76%) of 33 patients (all were grade 1 or 2), and neurotoxicities in three patients (one grade 2 and one grade 3 ICANSs and one grade 3 headache).Anti-GPRC5D CAR T-cell therapy showed an encouraging clinical efficacy and manageable safety profile in patients with R/R MM. For patients with MM that progressed after anti-BCMA CAR T-cell therapy or that is refractory to anti-BCMA CAR T cell, anti-GPRC5D CAR T-cell therapy might be a potential alternative option.
Reduced Thoracic Aortic Distensibility Upon Breast Cancer Diagnosis (WF-97415 and WF-98213)
Authors: Suhas Suddala, Nathaniel O’Connell, Ralph D’Agostino, Amy Ladd, Alexander R. Lucas, Jennifer H. Jordan, Fadi N. Salloum, Bonnie Ky, Mary Helen Hackney, W. Gregory Hundley
Journal: JACC CardioOncology (2023)
Developing a Model for Cross-Institutional Educational Collaborations
Authors: Iva Minga, Tochukwu Okwuosa, Nausheen Akhter, Christopher Gans, Sunil Pauwaa, Javier Gomez-Valencia, Haseeb Ilias-Basha, Amit Pursnani, Aparna Kalyan, Jeanne M. DeCara
Journal: JACC CardioOncology (2023)

• The CCCR represents a collaborative educational platform. • The forum can be reproduced to foster the exchange of practical and scientific knowledge/experience. • The created environment enhances clinical knowledge applied to the care of cardio-oncology patients.
High-throughput organo-on-pillar (high-TOP) array system for three-dimensional ex vivo drug testing
Authors: Hye Ryeong Jun, Hyun Ju Kang, Sung Hun Ju, Jung Eun Kim, Sang Youl Jeon, Bosung Ku, Jae Jun Lee, Minsung Kim, Min Jeong Kim, Jung-Joo Choi, Joseph J. Noh, Hyun-Soo Kim, Jeong-Won Lee, Jin-Ku Lee, Dong Woo Lee
Journal: Biomaterials (2023)
Left Atrial Appendage Occlusion in Patients With Atrial Fibrillation and Cancer
Authors: Samuel A. Shabtaie, Nicholas Y. Tan, Robert C. Ward, Bradley R. Lewis, Eric H. Yang, David R. Holmes, Joerg Herrmann
Journal: JACC CardioOncology (2023)

The prevention of stroke in patients with atrial fibrillation (AF) and cancer is challenging because patients are at increased bleeding and thrombotic risk.